This invention concerns aqueous solutions of indolocarbazoles suitable for pharmaceutical use.
Indolocarbazoles exhibit useful antifungal, antimicrobial and antitumor properties. Some indolocarbazoles such as K-252a modulate neurotrophin responses by affecting protein kinase activity (Berg et al. J. Biol. Chem. 267:13-16 (1992)). Indolocarbazoles can be isolated from a wide variety of microorganisms including S. staurosporeus, N. aerocoligenes, Actinomadura and Nocardiopsis sp using known methods (Kase et al., BBRC 142:436-440, (1987)). The synthetic preparation of several indolocarbazoles has been described (U.S. Pat. Nos. 4,923,986; 4,877,776; 5,093,330, each incorporated by reference herein; Moody et al., J. Org. Chem. 57:2105-2114 (1992), WO 93/08809). Several indolocarbazoles have been characterized and include, but are not limited to, staurosporine, rebeccamycin, (Moody et al., supra), K-252a, K-252b (Kase et al., supra), K-252c (also called staurosporine aglycon by Moody et al., supra), K-252d, and derivatives thereof (published Japanese patent applications 60-257652, 60-295172, 62-327858, 62-327859, and 60-295173).
Nakanishi et al. (J. Antibodies, 34:1066, (1986)) describe the insolubility of K-252a, K-252b, K-252c, and K-252d in water. U.S. Pat. No. 5,093,330 reports dry pharmaceutical preparations (dragees, tablets and capsules) of staurosporine derivatives that may contain polyethylene glycol and polyvinylpyrrolidone. U.S. Pat. No. 5,043,335 and WO 93/00909 each disclose pharmaceutical compositions including an indolocarbazole.